Abstract
The direct carcinogenic effects of sidestream (SS) and mainstream (MS) smoke condensates of a filtered commercial brand of blond cigarettes were compared using a lifetime mouse skin tumorigenicity assay on female NMRI mice. Each cigarette was smoked by a smoking machine under the standard conditions, and the separately collected SS and MS smoke condensates were extracted with acetone/methanol as described elsewhere. These were tested for carcinogenicity on an area of 1–1.5 cm shaved skin of mice on the lower back. The mice were treated with half of each dose (5, 10 or 15 mg) twice a week, for only 3 months. No substance was used as promoter or as an additional initiator of carcinogenicity. No statistically significant difference was found when the life spans of MS-treated and untreated animals were compared. In contrast, the life spans of SS-treated mice were significantly (P<0.01) shorter than those of MS-treated animals or those of all three negative control groups together. The observed carcinogenic effects were based on tumours and lesions found only on the site of application of the test material. Of 210 mice (effective number, 129) serving as the negative controls, 3 developed skin lesions but no tumours. Of 210 MS-treated mice (effective number, 177), 7 developed tumours (4 malignant and 3 benign) and 35 had a uniform type of precancerous skin lesions. The numbers of tumours or lesions were not increased dose-dependently. Of 210 SS-treated animals (effective number, 182), 30 developed tumours (16 malignant and 14 benign) and 56 had a uniform type of precancerous skin lesion. The initiation of these latter lesions was found to be dose-dependent (P<0.001).The SS-treated animals developed two to six times more skin tumours than the MS-treated mice. Comparing the negative controls with the MS- or SS-treated animals, the overall carcinogenic effect observed was statistically significant. Comparing the MS- with SS-treated animals, the overall carcinogenic effect of SS was much higher than that of MS (P<0.001).
Key words: Tobacco smoke condensate, Mainstream smoke, Sidestream smoke, Passive smoking, Mouse skin tumorigenicity
Abbreviations
- MS
mainstream
- SS
sidestream
References
- Bernfeld P, Homburger F, Soto E, Pai KJ (1979) Cigarette smoke inhalation studies in inbred Syrian golden hamsters. JNCI 63:675–689 [DOI] [PubMed] [Google Scholar]
- Bomhard E, Mohr U (1989) Spontaneous tumors in NMRI mice from carcinogenicity studies. Exp Pathol 36:129–145 [DOI] [PubMed] [Google Scholar]
- Brosch A (1900) Theoretische und experimentelle Untersuchungen zur Pathogenesis und Histogenesis der malignen Geschwülste. Virchows Arch A Pathol Anat Histol 162:32–84 [Google Scholar]
- Campbell JA (1936) The effects of exhaust gases from internal combustion engines and of tobacco smoke upon mice, with special reference to incidence of tumors of the lung. Br J Exp Pathol 17:146–158 [Google Scholar]
- Campbell JA (1939) Carcinogenic agents present in the atmosphere and incidence of primary lung tumors in mice. Br J Exp Pathol 20:122–132 [Google Scholar]
- Chortyk OT, Baker JL, Chamberlain WJ (1988) Selenium-mediated reduction in the mutagenicity of cigarette smoke. Environ Mol Mutagen 11:369–378 [DOI] [PubMed] [Google Scholar]
- Claxton LD, Morin RS, Hughes TJ, Lewtas J (1989) A genotoxic assessment of environmental tobacco smoke using bacterial bioassays. Mutat Res 222:81–99 [DOI] [PubMed] [Google Scholar]
- Day TD (1967) Carcinogenic action of cigarette smoke condensate on mouse skin: an attempt at a quantitative study. Br J Cancer 21:56–81 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dontenwill W, Elmenhorst H, Barker HP, Reckzeh G, Weber KH, Misfeld J, Timm J (1970a) Experimentelle Untersuchungen über die tumorerzeugende Wirkung von Zigarettenrauch-Kondensaten an der Mäusehaut. I. Mitteilung: Gesamtversuch. Z Krebsforsch 73:265–284 [PubMed] [Google Scholar]
- Dontenwill W, Elmenhorst H, Harker HP, Reckzeh G, Weber KH, Misfeld J, Timm J (1970b) Experimentelle Untersuchungen über die tumorerzeugende Wirkung von Zigarettenrauch-Kondensaten an der Mäusehaut. II. Mitteilung: Einzelvergleiche zwischen den Kondensaten modifizierter Zigaretten. Z Krebsforsch 73:285–304 [PubMed] [Google Scholar]
- Dontenwill W, Elmenhorst H, Harker HP, Reckzeh G, Weber KH, Misfeld J, Timm J (1970c) Experimentelle Untersuchungen über die tumorerzeugende Wirkung von Zigarettenrauch-Kondensaten an der Mäusehaut. III. Mitteilung: Untersuchungen zur Indentifizierung und Anreicherung tumorauslösender Fraktionen. Z Krebsforsch 73:305–314 [PubMed] [Google Scholar]
- Dontenwill W, Chevalier Hj, Harke HP, Lafrenz U, Reckzeh G, Schneider B (1973) Investigations on the effects of chronic cigarette-smoke inhalation in Syrian golden hamsters. JNCI 51:1781–1832 [DOI] [PubMed] [Google Scholar]
- Essenberg JM (1952) Cigarette smoke and the incidence of primary neoplasm of the lung in the albino mouse. Science 116:561–562 [DOI] [PubMed] [Google Scholar]
- Flory CM (1941) The production of tumors by tobacco tars. Cancer Res 1:262–276 [Google Scholar]
- Gart JJ, Tarone RE (1987) On the efficiency of age-adjusted tests in animal carcinogenicity experiments. Biometrics 43:235–244 [PubMed] [Google Scholar]
- Grimmer G, Böhnke H, Harke HP (1977) Passive smoking: measuring of concentrations of polycyclic aromatic hydrocarbons in rooms after machine smoking of cigarettes. Int Arch Occup Environ Health 40:83–92 [DOI] [PubMed] [Google Scholar]
- Grimmer G, Naujack KW, Dettbarn G (1987) Gaschromatographic determination of polycyclic aromatic hydrocarbons, azoarenes, aromatic amines in the particle and vapor phase of mainstream and sidestream smoke of cigarettes. Toxicol Lett 35:117–124 [DOI] [PubMed] [Google Scholar]
- Helwig C (1928) The growth-producing effects of extracts of tobacco on mice. JAMA 91:150–151 [Google Scholar]
- Hoffmann D, Wynder EL (1971) A study of tobacco carcinogenesis. XI. Tumor initiators, tumor accelerators, and tumor promoting activity of condensate fractions. Cancer 27:848–864 [DOI] [PubMed] [Google Scholar]
- Hoffmann D, Wynder EL, Riverson A, La Voie EJ, Hecht SS (1983) Skin bioassays in tobacco carcinogenesis. Prog Exp Tumor Res 26:43–67 [DOI] [PubMed] [Google Scholar]
- Hoffmann D, Adams JD, Brunnemann KD (1987) A critical look at N-nitrosamines in environmental tobacco smoke. Toxicol Lett 35:1–8 [DOI] [PubMed] [Google Scholar]
- Hoffmann E, Schreus HT, Zurhelle E (1923) Beobachtungen zur experimentellen Geschwulsterzeugung durch Teer verschiedener Herkunft und Paraffin. Dtsch Med Wochenschr 49:633–634 [Google Scholar]
- Homburger F, Treger A, Baker JR (1963) Mouse-skin painting with smoke condensates from cigarettes made of pipe, cigar, and cigarette tobaccos. JNCI 31:1445–1459 [PubMed] [Google Scholar]
- IARC (1986) Evaluation of the carcinogenic risk of chemicals to humans: tobacco smoking. International Agency for Research on Cancer, vol 38. Lyon, France, pp 127–198 [Google Scholar]
- Karube T, Odagiri Y, Takemoto K, Watanabe S (1989) Analyses of transplacentally induced sister chromatid exchanges and micronuclei in mouse fetal liver cells following maternal exposure to cigarette smoke. Cancer Res 49:3550–3552 [PubMed] [Google Scholar]
- Löfroth G, Lazaridis G (1986) Environmental tobacco smoke: comparative characterization by mutagenicity assays of sidestream and mainstream cigarette smoke. Environ Mutagen 8:693–704 [DOI] [PubMed] [Google Scholar]
- Mohtashamipur E, Norpoth K, Heger M (1984) Urinary excretion of frameshift mutagens in rats caused by passive smoking. J Cancer Res Clin Oncol 108:296–301 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mohtashamipur E, Steinforth T, Norpoth K (1988) Comparative bone marrow clastogenicity of cigarette sidestream, mainstream and recombined smoke condensates in mice. Mutagenesis 3:419–422 [DOI] [PubMed] [Google Scholar]
- Monteith, LG, Simmons DM, Davis KH, Keever TJ, Callahan JC, Hughes TJ, Claxton LD (1986) Mutagenic activity of sidestream and mainstream cigarette smoke in the Ames/Salmonella assay (abstract). Environ Mutagen 8 (suppl 6):56 [Google Scholar]
- Munoz N, Correra P, Bock FG (1968) Comparative carcinogenic effect of two types of tobacco. Cancer 21:376–389 [DOI] [PubMed] [Google Scholar]
- Roffo AH (1931) Durch Tabak beim Kaninchen entwickeltes Carcinom. Z Krebsforsch 33:321–332 [Google Scholar]
- Roffo AH (1939) Krebserzeugende Einheit der verschiedenen Tabakteere. Dtsch Med Wochenschr 65:963–967 [Google Scholar]
- Sachs L (1978) Angewandte Statistik. Springer, Berlin Heidelberg New York, S 230–238 [Google Scholar]
- Schürch O, Winterstein A (1935) Experimentelle Untersuchungen zur Frage Tabak und Krebs. Z Krebsforsch 42:76–92 [Google Scholar]
- Schürch O, Winterstein A (1937) Experimenteller Beitrag zur Frage Tabak und Krebs. Z Krebsforsch 46:414–419 [Google Scholar]
- Wacker L, Schmincke A (1911) Experimentelle Untersuchungen zur kausalen Genese atypischer Epithelwucherungen. Münchn Med Wochenschr 58:1607–1613 [Google Scholar]
- Wynder EL, Hoffmann D (1959) A study od tobacco carcinogenesis. VII. The role of higher polycyclic hydrocarbons. Cancer 12:1079–1086 [DOI] [PubMed] [Google Scholar]
- Wynder EL, Hoffmann D (1968) Experimental tobacco carcinogenesis. Science 162:862–871 [DOI] [PubMed] [Google Scholar]
- Wynder EL, Graham EA, Croninger AB (1953) Experimental production of carcinoma with cigarette tar. Cancer Res 13:855–864 [PubMed] [Google Scholar]
- Wynder EL, Kopf P, Ziegler H (1957) A study of tobacco carcinogenesis. II. Dose-response studies. Cancer 10:1193–1200 [DOI] [PubMed] [Google Scholar]
